- Email: [email protected]
European ADNI
Abstracts / Neurobiology of Aging 39 (2016) S1eS31
cases. Time-trends and intervention studies have confirmed these findings. In addition, potential effects of preventive interventions have been estimated. However, our current knowledge lacks several pieces especially related to the interactions between genes and environmental factors acting at different times in life. We can increase the already substantial proportion of preventable AD cases by taking into account the interaction between genetic and non-genetic factors. Emerging evidence suggests that a low vascular burden and a healthy life style may modulate the genetic susceptibility due to the APOE gene, as well as specific factors such as physical activity and education. In addition, the effect of several risk factors seems to be potentiated in APOE e4 carriers. Unfortunately regarding dementia risk, evidence on gene-environment beyond APOE is scarce whereas much more has been done in cognitive aging. The effects of genetic variations on cognition, brain structure and brain function become stronger as people age, suggesting that older people are more vulnerable to disadvantageous genotypes of different candidate genes. This vulnerability could be linked to multiple environmental exposures. In summary, although each individual carries a unique pattern of genetic, physiologic, psychological and environmental determinants, it is possible to identify and personalize some new preventive strategies by taking into account the interplay between genetic and environmental determinants to AD and dementia pathogenesis. Keyword. Gene-environment interaction
A CLINICAL TRIAL INVESTIGATING THE EFFECTS OF FORTASYN CONNECT (SOUVENAID) IN PRODROMAL ALZHEIMER’S DISEASE: RESULTS OF THE LIPIDIDIET STUDY Hilkka Soininen1, Pieter Visser2, Miia Kivipelto3, Tobias Hartmann4 for the LipiDiDiet study group. 1 University of Eastern Finland, Kuopio, Finland; 2 Vrije Universiteit University Medical Center, Amsterdam, Netherlands; 3 Karolinska Institutet, Huddinge, Sweden; 4 Deutsches Institut fuer Demenz Praevention, Homburg, Germany. E-mail: hilkka.soininen@uef.fi The specific nutrient combination Fortasyn1 Connect is present in Souvenaid1, a Food for Special Medical Purposes (FSMP) for the dietary management of early Alzheimer’s disease. Extensive preclinical investigation, much of which took place in the LipiDiDiet programme2 indicated that this nutrient combination has effects on multiple biological pathways that contribute to an overall neuroprotective effect. Earlier randomised controlled trials (RCTs) with this intervention have shown an improved memory performance in drug-naïve mild AD patients, and an excellent safety profile. Together these data suggest that this nutritional approach is a suitable candidate for early intervention, providing the rationale for the LipiDiDiet study2, which was designed to investigate the effects in prodromal AD. The LipiDiDiet study (NTR1705) was a 24-month, double-blind, parallel-group, multi-centre, multi-country RCT in subjects with prodromal AD (criteria Dubois et al., 2007), receiving the nutrition combination or an iso-caloric control product once daily. Main study visits took place at baseline, 6, 12 and 24 months. Primary outcome was a cognitive function composite score (z-score) based on five items from a modified neuropsychological test battery (mNTB): CERAD 10-word immediate recall, delayed recall and recognition, category fluency and letter digit substitution test. Secondary- and exploratory outcomes included the memory domain from the mNTB, MRI brain atrophy rates, CDR-SOB, other cognitive and laboratory parameters, and tolerance and safety. After completion of the 24-month RCT subjects were offered optional successive 12-month double blind extension studies. The 24-month RCT was completed in 2015, and the majority of the eligible study completers opted to continue for each extension year. First results on the main outcomes of the 24-month RCT will be presented at the conference.1 Fortasyn and Souvenaid are registered trademarks of N.V. Nutricia2 Funded by the EU FP7 project LipiDiDiet, Grant Agreement N 211696. Keywords. Alzheimer’s disease, Biomarker, Intervention, Lipid, Nutrient, Imaging
S23
Age represents the main risk factor for dementia. It has been estimated that nearly 30% of elderly individuals over 85 years of age or older in Europe have been diagnosed with dementia. Similarly to individuals of the same age, elderly patients with dementia are characterized by multimorbidity and they need to take several medications during the day. These conditions are coupled with the expected cognitive, functional and behavioral impairment of dementia patients leading to a high health and social care demand. Modern geriatrics provide a model of care that is based on comprehensive geriatric assessment (CGA) and multidisciplinary intervention. Such approach appears to be the best model to provide appropriate care and to target the complex needs of patients with dementia. In particular, scientific evidence indicates that the highest advantages for patients are reached when the comprehensive and multidisciplinary approach is not only adopted for the assessment of patients but also at the time of implementing the planned intervention and later for the evaluation of results. The CGA provides an evaluation of the different ’dimensions’ of the person affected by dementia including cognitive and functional status, behavior, mood, comorbidities, socio-economic status, caregiver condition. The CGA is performed using comprehensive and standardized assessment tools that have been specifically developed for the assessment of patients with dementia. Such tools provide data to assist clinical decisions leading to the development of an individualized plan that is tailored on the individual needs. The systematic use of standardized CGA tools has led to the creation of highquality databases that are currently available for clinical research and for quality of care control programs and to assist health care resources allocation. Keywords. Comprehensive geriatric assessment, Dementia, Multimorbidity
CAN MRI MEASURE DRUG EFFICACY? BRAIN MRI STUDIES IN IMI PHARMACOG WP5 / EUROPEAN ADNI Giovanni Frisoni. IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy. E-mail: [email protected] Background. The current model of typical Alzheimer’s disease (AD) assumes that brain amyloidosis biomarkers (abnormal PIB-PET retention or low Ab42 concentration in cerebrospinal fluid, CSF) appear in the earliest stages of the disease. Workpackage5 of PharmaCog (E-ADNI) is a serial multicenter European study aimed to identify new biomarkers of disease progression in 145 patients with amnestic mild cognitive impairment (aMCI). These patients underwent clinical and neuropsychological evaluation, MRI, EEG, CSF and blood collection for at least 2 years. Aim of this study is to investigate the effects of amyloid on brain MRI structural alterations at baseline and after 1 year. Methods. CSF concentration of Ab42 and tau phosphorylated at residue 181 (p-tau) were performed using ELISA kits. Volumes were computed using Freesurfer. Diffusion metrics such as fractional anisotropy (FA), axial, radial and mean diffusivity (respectively AxD, RD and MD) were extracted using an atlas-based approach. Results. Baseline atrophy in the hippocampus, parietal and temporal cortices was reported in Ab+ relative to Ab- patients. Moreover, hippocampus and right temporal cortex of Ab+ positive patients became increasingly atrophic with AD progression. Baseline diffusion analysis reported a significant alterations of all the diffusion metrics in the splenium of the corpus callosum (p<0.05) of Ab+ relative to Ab- patients while no significant longitudinal diffusion changes were observed. Of note, p-tau and not amyloid, altered the longitudinal diffusion features in many tracts considered. Conclusions. These preliminary longitudinal data suggest that in aMCI patients i) amyloid pathology affects the grey and white matter microstructure at earliest stages; ii) amyloid pathology contributes to hippocampal and temporal cortex degeneration; iii) neurodegeneration and not amyloid pathology contributes to white matter diffusion deterioration. Longitudinal analysis is still ongoing. Pharmacog is funded by the EU-FP7 for the Innovative Medicine Initiative (grant n 115009). Keywords. Amnesia, Amyloid, Mild cognitive impairment, MRI
MOLECULAR PET IMAGING AS CORRELATES TO DRUG RESPONSE CARING FOR COMPLEX OLDER PATIENTS: THE INFLUENCE OF COGNITIVE STATUS
Agneta Nordberg. Karolinska Institutet, Stockholm, Sweden. E-mail: [email protected]
Roberto Bernabei. Università Cattolica, Rome, IT. E-mail: [email protected]
The rapid development of molecular imaging techniques provide new tools to detect early pathological changes in brain and understand time course and the
cases. Time-trends and intervention studies have confirmed these findings. In addition, potential effects of preventive interventions have been estimated. However, our current knowledge lacks several pieces especially related to the interactions between genes and environmental factors acting at different times in life. We can increase the already substantial proportion of preventable AD cases by taking into account the interaction between genetic and non-genetic factors. Emerging evidence suggests that a low vascular burden and a healthy life style may modulate the genetic susceptibility due to the APOE gene, as well as specific factors such as physical activity and education. In addition, the effect of several risk factors seems to be potentiated in APOE e4 carriers. Unfortunately regarding dementia risk, evidence on gene-environment beyond APOE is scarce whereas much more has been done in cognitive aging. The effects of genetic variations on cognition, brain structure and brain function become stronger as people age, suggesting that older people are more vulnerable to disadvantageous genotypes of different candidate genes. This vulnerability could be linked to multiple environmental exposures. In summary, although each individual carries a unique pattern of genetic, physiologic, psychological and environmental determinants, it is possible to identify and personalize some new preventive strategies by taking into account the interplay between genetic and environmental determinants to AD and dementia pathogenesis. Keyword. Gene-environment interaction
A CLINICAL TRIAL INVESTIGATING THE EFFECTS OF FORTASYN CONNECT (SOUVENAID) IN PRODROMAL ALZHEIMER’S DISEASE: RESULTS OF THE LIPIDIDIET STUDY Hilkka Soininen1, Pieter Visser2, Miia Kivipelto3, Tobias Hartmann4 for the LipiDiDiet study group. 1 University of Eastern Finland, Kuopio, Finland; 2 Vrije Universiteit University Medical Center, Amsterdam, Netherlands; 3 Karolinska Institutet, Huddinge, Sweden; 4 Deutsches Institut fuer Demenz Praevention, Homburg, Germany. E-mail: hilkka.soininen@uef.fi The specific nutrient combination Fortasyn1 Connect is present in Souvenaid1, a Food for Special Medical Purposes (FSMP) for the dietary management of early Alzheimer’s disease. Extensive preclinical investigation, much of which took place in the LipiDiDiet programme2 indicated that this nutrient combination has effects on multiple biological pathways that contribute to an overall neuroprotective effect. Earlier randomised controlled trials (RCTs) with this intervention have shown an improved memory performance in drug-naïve mild AD patients, and an excellent safety profile. Together these data suggest that this nutritional approach is a suitable candidate for early intervention, providing the rationale for the LipiDiDiet study2, which was designed to investigate the effects in prodromal AD. The LipiDiDiet study (NTR1705) was a 24-month, double-blind, parallel-group, multi-centre, multi-country RCT in subjects with prodromal AD (criteria Dubois et al., 2007), receiving the nutrition combination or an iso-caloric control product once daily. Main study visits took place at baseline, 6, 12 and 24 months. Primary outcome was a cognitive function composite score (z-score) based on five items from a modified neuropsychological test battery (mNTB): CERAD 10-word immediate recall, delayed recall and recognition, category fluency and letter digit substitution test. Secondary- and exploratory outcomes included the memory domain from the mNTB, MRI brain atrophy rates, CDR-SOB, other cognitive and laboratory parameters, and tolerance and safety. After completion of the 24-month RCT subjects were offered optional successive 12-month double blind extension studies. The 24-month RCT was completed in 2015, and the majority of the eligible study completers opted to continue for each extension year. First results on the main outcomes of the 24-month RCT will be presented at the conference.1 Fortasyn and Souvenaid are registered trademarks of N.V. Nutricia2 Funded by the EU FP7 project LipiDiDiet, Grant Agreement N 211696. Keywords. Alzheimer’s disease, Biomarker, Intervention, Lipid, Nutrient, Imaging
S23
Age represents the main risk factor for dementia. It has been estimated that nearly 30% of elderly individuals over 85 years of age or older in Europe have been diagnosed with dementia. Similarly to individuals of the same age, elderly patients with dementia are characterized by multimorbidity and they need to take several medications during the day. These conditions are coupled with the expected cognitive, functional and behavioral impairment of dementia patients leading to a high health and social care demand. Modern geriatrics provide a model of care that is based on comprehensive geriatric assessment (CGA) and multidisciplinary intervention. Such approach appears to be the best model to provide appropriate care and to target the complex needs of patients with dementia. In particular, scientific evidence indicates that the highest advantages for patients are reached when the comprehensive and multidisciplinary approach is not only adopted for the assessment of patients but also at the time of implementing the planned intervention and later for the evaluation of results. The CGA provides an evaluation of the different ’dimensions’ of the person affected by dementia including cognitive and functional status, behavior, mood, comorbidities, socio-economic status, caregiver condition. The CGA is performed using comprehensive and standardized assessment tools that have been specifically developed for the assessment of patients with dementia. Such tools provide data to assist clinical decisions leading to the development of an individualized plan that is tailored on the individual needs. The systematic use of standardized CGA tools has led to the creation of highquality databases that are currently available for clinical research and for quality of care control programs and to assist health care resources allocation. Keywords. Comprehensive geriatric assessment, Dementia, Multimorbidity
CAN MRI MEASURE DRUG EFFICACY? BRAIN MRI STUDIES IN IMI PHARMACOG WP5 / EUROPEAN ADNI Giovanni Frisoni. IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy. E-mail: [email protected] Background. The current model of typical Alzheimer’s disease (AD) assumes that brain amyloidosis biomarkers (abnormal PIB-PET retention or low Ab42 concentration in cerebrospinal fluid, CSF) appear in the earliest stages of the disease. Workpackage5 of PharmaCog (E-ADNI) is a serial multicenter European study aimed to identify new biomarkers of disease progression in 145 patients with amnestic mild cognitive impairment (aMCI). These patients underwent clinical and neuropsychological evaluation, MRI, EEG, CSF and blood collection for at least 2 years. Aim of this study is to investigate the effects of amyloid on brain MRI structural alterations at baseline and after 1 year. Methods. CSF concentration of Ab42 and tau phosphorylated at residue 181 (p-tau) were performed using ELISA kits. Volumes were computed using Freesurfer. Diffusion metrics such as fractional anisotropy (FA), axial, radial and mean diffusivity (respectively AxD, RD and MD) were extracted using an atlas-based approach. Results. Baseline atrophy in the hippocampus, parietal and temporal cortices was reported in Ab+ relative to Ab- patients. Moreover, hippocampus and right temporal cortex of Ab+ positive patients became increasingly atrophic with AD progression. Baseline diffusion analysis reported a significant alterations of all the diffusion metrics in the splenium of the corpus callosum (p<0.05) of Ab+ relative to Ab- patients while no significant longitudinal diffusion changes were observed. Of note, p-tau and not amyloid, altered the longitudinal diffusion features in many tracts considered. Conclusions. These preliminary longitudinal data suggest that in aMCI patients i) amyloid pathology affects the grey and white matter microstructure at earliest stages; ii) amyloid pathology contributes to hippocampal and temporal cortex degeneration; iii) neurodegeneration and not amyloid pathology contributes to white matter diffusion deterioration. Longitudinal analysis is still ongoing. Pharmacog is funded by the EU-FP7 for the Innovative Medicine Initiative (grant n 115009). Keywords. Amnesia, Amyloid, Mild cognitive impairment, MRI
MOLECULAR PET IMAGING AS CORRELATES TO DRUG RESPONSE CARING FOR COMPLEX OLDER PATIENTS: THE INFLUENCE OF COGNITIVE STATUS
Agneta Nordberg. Karolinska Institutet, Stockholm, Sweden. E-mail: [email protected]
Roberto Bernabei. Università Cattolica, Rome, IT. E-mail: [email protected]
The rapid development of molecular imaging techniques provide new tools to detect early pathological changes in brain and understand time course and the