- Email: [email protected]
CSF STREM2 LEVELS INCREASE IN EARLY STAGES OF AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE (ADAD) AND ARE ASSOCIATED WITH MARKERS OF NEURONAL INJURY
Podium Presentations: Thursday, July 28, 2016
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When limiting analyses to presymptomatic carriers the changes seen are similar anatomically but to a lesser degree. There appears be a non-linear timecourse of atrophy over a long preclinical period: atrophy rates in presymptomatic carriers deviated from non-carriers, in a region-dependent manner from 1 to 7 years before expected age at onset. Conclusions: Structural MRI can detect pathological change several years before expected onset; atrophy patterns are influenced by genetic mutation. Serial MRI may be used to track atrophy progression in presymptomatic familial AD. F5-02-03
BDNF VAL66MET MODERATES COGNITIVE IMPAIRMENT, NEURONAL DYSFUNCTION AND TAU IN PRECLINICAL AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE
Yen Ying Lim1, Jason Hassenstab2, Carlos Cruchaga3, Alison M. Goate4,5, Anne M. Fagan6, Tammie Lee Smith Benzinger6, Paul Maruff7,8, Peter J. Snyder9, Colin L. Masters10, Allegri Ricardo11, Jasmeer P. Chhatwal12, Martin R. Farlow13, Neill R. Graff-Radford14, Christoph Laske15, Johannes Levin16, Eric McDade17, John M. Ringman18, Martin N. Rossor19, Stephen Salloway20, Peter W. Schofield21, David M. Holtzman6, John C. Morris2, Randall Bateman22, 1The Florey Institute, The University of Melbourne, Parkville, Australia; 2Washington University in St. Louis, St. Louis, MO, USA; 3Washington University in St. Louis, Saint Louis, MO, USA; 4Icahn School of Medicine at Mount Sinai, New York, NY, USA; 5Washington University, Saint Louis, MO, USA; 6 Washington University School of Medicine, St. Louis, MO, USA; 7Cogstate Ltd., Melbourne, Australia; 8The Florey Institutes of Neurosciences and Mental Health, Melbourne, Australia; 9Alpert Medical School of Brown University, Providence, RI, USA; 10The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; 11Instituto de Investigaciones Neurologicas, Buenos Aires, Argentina; 12Massachusetts General Hospital and the Athinoula A Martinos Center for Biomedical Imaging, Boston, MA, USA; 13Indiana University School of Medicine, Indianapolis, IN, USA; 14 Mayo Clinic, Jacksonville, FL, USA; 15Department of Psychiatry and Psychotherapy, University of T€ubingen, T€ubingen, Germany; 16University of Munich, Munich, Germany; 17Washington University at St. Louis, St. Louis, MO, USA; 18Keck School of Medicine at USC, Los Angeles, CA, USA; 19 UCL Institute of Neurology, London, United Kingdom; 20Butler Hospital & Alpert Medical School of Brown University, Providence, RI, USA; 21 University of Newcastle, Newcastle, Australia; 22Washington University in St. Louis, St Louis, MO, USA. Contact e-mail: [email protected] Background: The brain-derived neurotrophic factor (BDNF) Val66-
Met polymorphism has been implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate Ab-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer’s disease (AD). However, the effect of BDNF in autosomal dominant AD (ADAD) is unknown. We investigated the effect of BDNF Val66Met on cognitive function, glucose metabolism, tau and Ab in preclinical ADAD. As the apolipoprotein E (APOE) ε4 allele has also previously been shown to interact with BDNF in sporadic AD, we also explored for similar interaction of 34 in ADAD. Methods: Baseline clinical, neuropsychological, genetic, biomarker and neuroimaging data from the Dominantly Inherited Alzheimer Network (DIAN) were analyzed in 131 mutation non-carriers (NC) and 143 preclinical ADAD mutation carriers (MC), an average 12 years prior to clinical symptom onset. BDNF genotype data were obtained for MCs (95 Val66 homozygotes, 48 Met66 carriers). Results: Among preclinical MCs, Met66 carriers had worse memory performance, lower glucose metabolism and increased levels of cerebrospinal fluid (CSF) tau and phosphorylated tau (p-tau181) when compared to Val66 homozygotes (Figure 1). Cortical Ab and CSF Ab42 levels did not significantly differ between preclinical MC Val66 homozygotes and Met66 carriers (Figure
Figure 1. Magnitude of abnormality in episodic memory performance, and markers of Ab, phosphorylated tau and glucose metabolism in preclinical MC Val66 homozygotes and preclinical MC Met66 carriers when compared to mutation non-carriers (error bars represent 95% confidence intervals).
1). There was an effect of APOE on Ab levels but not cognitive function, glucose metabolism or tau. There were no significant interactions between APOE and BDNF on any biomarker or cognitive outcome measure. Conclusions: As in sporadic AD, the deleterious effects of Ab on cognitive function, glucose metabolism and tau in preclinical ADAD mutation carriers are less in Val66 homozygotes. The results suggest that allelic variation in BDNF and APOE may affect different AD processes with ε4 increasing cortical Ab accumulation and Met66 moderating cognitive impairment and neuronal dysfunction through tau. To date, this is the only genetic factor found to moderate downstream effects of Ab in ADAD, and has implications for clinical trial designs. F5-02-04
CSF STREM2 LEVELS INCREASE IN EARLY STAGES OF AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE (ADAD) AND ARE ASSOCIATED WITH MARKERS OF NEURONAL INJURY
Christian Haass1, Marc Suarez-Calvet2, Gernot Kleinberger3, Miguel Angel Araque Caballero4, Michael Ewers5, 1German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; 2 Ludwig-Maximilians-University, Munich, Germany; 3 Ludwig-Maximilians-University Munich, Munich, Germany; 4Institute for Stroke and Dementia Research, M€unchen, Germany; 5Institute for Stroke and Dementia Research, Klinikum der Universitaet Muenchen, Ludwig-Maximilians-University Munich, Munich, Germany. Contact e-mail: [email protected] Background: TREM2 is a transmembrane protein selectively ex-
pressed by microglia in the central nervous system. The TREM2 ectodomain is proteolytically released as a soluble variant (sTREM2). sTREM2 in the cerebrospinal fluid (CSF) may be a candidate for a marker of microglial activity. We previously described that CSF sTREM2 is increased in early symptomatic stages of sporadic Alzheimer’s disease (AD), but nothing is known in autosomal dominant Alzheimer’s disease (ADAD). In the present study, we aimed to determine how many years before the expected symptom onset (EYO) mutation carriers (MC) of ADAD show altered CSF sTREM2 levels compared to non-carriers (NC). Methods: We analyzed data from 218 participants, including 127 MC and 91 NC siblings enrolled in the Dominantly Inherited Alzheimer Network (DIAN) initiative. In order to study the changes of CSF sTREM2 during the progression of AD, we used a linear mixed model with mutation status, EYO (and its quadratic term and the
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Podium Presentations: Thursday, July 28, 2016
interactions with mutation status) along with age as fixed effects, and family affiliation as random effect. To determine differences between MC and NC, we estimated the levels of CSF sTREM2 at 5-years intervals of EYO from the previous model, and subsequently compared them by t-test. Associations with the core AD CSF biomarkers were assessed using a linear regression model adjusted for gender, age and EYO. Results: CSF sTREM2 levels were significantly increased in MC compared to NC at EYO¼-10 and these difference remained significant until EYO¼ +5 years. In more advanced stages (EYO>+5), no significant differences were found. In the whole sample of subjects, higher levels of CSF sTREM2 were associated with higher levels of T-tau (b¼+0.302, p<0.0001) and P-tau181P (b¼+0.274, p¼0.0001), but no significant association was found with Ab 1-42 (b¼+0.008, p¼0.904). The positive association between CSF sTREM2 and Ttau or P-tau181Pwas present in NC and asymptomatic (CDR¼0) MC subjects but not in the symptomatic (CDR>0) MC ones. Conclusions: CSF sTREM2 levels change during disease progression of ADAD, with an increase that occurs years before the symptoms onset (possibly reflecting an early increased microglia response to neuronal injury) and is attenuated in later stages. THURSDAY, JULY 28, 2016 FEATURED RESEARCH SESSIONS F5-03 DEBATE: SHOULD BIOMARKERS EVER BE USED IN CLINICAL CARE? F5-03-01
BIOMARKERS SHOULD BE USED IN CLINICAL CARE BASED ON EXISTING EFFECTIVENESS AND ECONOMIC EVIDENCE
Michel Louis Grignon, McMaster University, Hamilton, ON, Canada. Contact e-mail: [email protected] Background: Funding agencies are allocating large amounts of their resources to support biomarker research. Methods: Commentaries and reviews were identified through a literature review. Results: Biomarkers of dementia should be used in clinical care for the four main following reasons: (1) We need biomarkers (mostly MRI) to rule out other possible causes of cognitive impairment such as strokes or brain injuries. This one is obvious and not disputed. (2) Biomarkers should be used for early detection, before Alzheimer’s disease has already brought irreversible damages to the brain. The logic of the argument is Bayesian: even though the sensitivity and specificity of existing tests are low (Noel-Storr et al. 2013), the costs of wrong diagnoses are small, and the benefits of a true positive are very large. The main reason is that prevention after early detection involves mostly lifestyle changes, that have minor side effects only. (3) Biomarkers should be used in clinical settings, because otherwise they will be used outside of the clinical encounter: individuals want to know and if the information is potentially available, they will get the information and, potentially act upon it. Insurers and employers might also force individuals to produce the information. Keeping such valuable information within the confine of the clinical encounter will be socially and clinically welfare-improving. (4) Last, current trials are too small and narrow in focus to provide good evidence on their accuracy. Real-life use of tests in clinical practice will yield the scale and scope needed for validating and improving tests. Moreover, since blinding is not achieved in trials for dementia, real-life tests will do as well as RCTs. Conclusions: Clinical care in 2016 is justified in using the available biomarkers. References:Anna Noel-Storr et al. (2013) “Systematic review of the body of evidence for the use of bio-
markers in the diagnosis of dementia”, Alzheimer’s and Dementia, 9(3), e96-e105, http://www.alz.org/research/. F5-03-02
BIOMARKERS ARE USEFUL IN TERTIARY CARE CLINICAL DECISION-MAKING
Howard H. Feldman, University of British Columbia, Vancouver, BC, Canada. Contact e-mail: [email protected] Background: Pathophysiological Alzheimer Disease (AD) bio-
markers including amyloid PET, and/or CSF measures of Abeta 1-42, total tau and phospho-tau should be used in tertiary clinical care. Methods: In the tertiary care setting, dementia specialists, in conjunction with trained radiologists at PET facilities, and/or labs with expertise in CSF assays can improve diagnostic accuracy and clinical management. There are benefits to patients and families that can be realized and now is the time to advance this diagnostic paradigm shift. Results: The clinical diagnostic accuracy of AD without pathophysiological biomarkers falls well short in sensitivity and specificity against the neuropathological gold standard. Atypical AD presentations are particularly challenging, without supportive in-vivo evidence of AD pathology. There are also 2030% of patients diagnosed AD who lack AD neuropathology1. These diagnostic challenges are amplified in trying to diagnose AD at the mild cognitive stage (MCI) when patients need vocational, social and prognostic guidance and accurate diagnosis matters. Research studies using CSF pathophysiological biomarkers achieve consistently higher AD diagnostic accuracy 2. In the tertiary care setting adding CSF biomarkers has been shown to improve diagnostic confidence, to assist diagnostic reclassification, and clinical decision making1. Conclusions: Adopting biomarkers more widely into tertiary clinical care will facilitate the necessary experience and pragmatic trials to refine their use, indications and health economic impact. References: Mouton-Liger F, Walton D, Troussiere AC et al; J.Neurol 2014, 261;144-151 2. Hansson O, Zetterberg H, Buchhave P, et al Lancet Neurol 2006; 5 (3) 228-234.
F5-03-03
‘PRIME TIME’ FOR FUNDING OF BIOMARKERS BY THIRD PARTY PAYERS AND GOVERNMENTS HAS NOT YET ARRIVED
Martin Richard John Knapp, London School of Economics and Political Science, London, United Kingdom. Contact e-mail: [email protected] Background: Enormous efforts are underway to identify biomarkers that will aid, target and improve the dementia diagnosis and treatment. Methods: Evidence is drawn from the dementia and (especially) other clinical fields on the healthcare system implications of developing and employing tests for biomarkers. Results: There are, rightly, major efforts today in many countries to ‘personalise’ how health and care systems respond to the circumstances, needs and preferences of individuals (e.g. ‘precision medicine’). But in the dementia field the state of development of biomarkers raises serious doubts about affordability and costeffectiveness, whether dementia care is funded by third party payers or governments. There are up-front costs associated with searching for any new technique or treatment; the costs of finding biomarkers, although initially mainly met by industry, will need to be recouped somewhere down the line in costs for healthcare providers and/or patients. There are the costs of the tests required to assess biomarkers; these costs could be acceptable so long as the tests are accurate and the treatments subsequently targeted are effective, available and affordable. If those tests are financially or logistically burdensome (to patients or clinicians) they could
P369
When limiting analyses to presymptomatic carriers the changes seen are similar anatomically but to a lesser degree. There appears be a non-linear timecourse of atrophy over a long preclinical period: atrophy rates in presymptomatic carriers deviated from non-carriers, in a region-dependent manner from 1 to 7 years before expected age at onset. Conclusions: Structural MRI can detect pathological change several years before expected onset; atrophy patterns are influenced by genetic mutation. Serial MRI may be used to track atrophy progression in presymptomatic familial AD. F5-02-03
BDNF VAL66MET MODERATES COGNITIVE IMPAIRMENT, NEURONAL DYSFUNCTION AND TAU IN PRECLINICAL AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE
Yen Ying Lim1, Jason Hassenstab2, Carlos Cruchaga3, Alison M. Goate4,5, Anne M. Fagan6, Tammie Lee Smith Benzinger6, Paul Maruff7,8, Peter J. Snyder9, Colin L. Masters10, Allegri Ricardo11, Jasmeer P. Chhatwal12, Martin R. Farlow13, Neill R. Graff-Radford14, Christoph Laske15, Johannes Levin16, Eric McDade17, John M. Ringman18, Martin N. Rossor19, Stephen Salloway20, Peter W. Schofield21, David M. Holtzman6, John C. Morris2, Randall Bateman22, 1The Florey Institute, The University of Melbourne, Parkville, Australia; 2Washington University in St. Louis, St. Louis, MO, USA; 3Washington University in St. Louis, Saint Louis, MO, USA; 4Icahn School of Medicine at Mount Sinai, New York, NY, USA; 5Washington University, Saint Louis, MO, USA; 6 Washington University School of Medicine, St. Louis, MO, USA; 7Cogstate Ltd., Melbourne, Australia; 8The Florey Institutes of Neurosciences and Mental Health, Melbourne, Australia; 9Alpert Medical School of Brown University, Providence, RI, USA; 10The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; 11Instituto de Investigaciones Neurologicas, Buenos Aires, Argentina; 12Massachusetts General Hospital and the Athinoula A Martinos Center for Biomedical Imaging, Boston, MA, USA; 13Indiana University School of Medicine, Indianapolis, IN, USA; 14 Mayo Clinic, Jacksonville, FL, USA; 15Department of Psychiatry and Psychotherapy, University of T€ubingen, T€ubingen, Germany; 16University of Munich, Munich, Germany; 17Washington University at St. Louis, St. Louis, MO, USA; 18Keck School of Medicine at USC, Los Angeles, CA, USA; 19 UCL Institute of Neurology, London, United Kingdom; 20Butler Hospital & Alpert Medical School of Brown University, Providence, RI, USA; 21 University of Newcastle, Newcastle, Australia; 22Washington University in St. Louis, St Louis, MO, USA. Contact e-mail: [email protected] Background: The brain-derived neurotrophic factor (BDNF) Val66-
Met polymorphism has been implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate Ab-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer’s disease (AD). However, the effect of BDNF in autosomal dominant AD (ADAD) is unknown. We investigated the effect of BDNF Val66Met on cognitive function, glucose metabolism, tau and Ab in preclinical ADAD. As the apolipoprotein E (APOE) ε4 allele has also previously been shown to interact with BDNF in sporadic AD, we also explored for similar interaction of 34 in ADAD. Methods: Baseline clinical, neuropsychological, genetic, biomarker and neuroimaging data from the Dominantly Inherited Alzheimer Network (DIAN) were analyzed in 131 mutation non-carriers (NC) and 143 preclinical ADAD mutation carriers (MC), an average 12 years prior to clinical symptom onset. BDNF genotype data were obtained for MCs (95 Val66 homozygotes, 48 Met66 carriers). Results: Among preclinical MCs, Met66 carriers had worse memory performance, lower glucose metabolism and increased levels of cerebrospinal fluid (CSF) tau and phosphorylated tau (p-tau181) when compared to Val66 homozygotes (Figure 1). Cortical Ab and CSF Ab42 levels did not significantly differ between preclinical MC Val66 homozygotes and Met66 carriers (Figure
Figure 1. Magnitude of abnormality in episodic memory performance, and markers of Ab, phosphorylated tau and glucose metabolism in preclinical MC Val66 homozygotes and preclinical MC Met66 carriers when compared to mutation non-carriers (error bars represent 95% confidence intervals).
1). There was an effect of APOE on Ab levels but not cognitive function, glucose metabolism or tau. There were no significant interactions between APOE and BDNF on any biomarker or cognitive outcome measure. Conclusions: As in sporadic AD, the deleterious effects of Ab on cognitive function, glucose metabolism and tau in preclinical ADAD mutation carriers are less in Val66 homozygotes. The results suggest that allelic variation in BDNF and APOE may affect different AD processes with ε4 increasing cortical Ab accumulation and Met66 moderating cognitive impairment and neuronal dysfunction through tau. To date, this is the only genetic factor found to moderate downstream effects of Ab in ADAD, and has implications for clinical trial designs. F5-02-04
CSF STREM2 LEVELS INCREASE IN EARLY STAGES OF AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE (ADAD) AND ARE ASSOCIATED WITH MARKERS OF NEURONAL INJURY
Christian Haass1, Marc Suarez-Calvet2, Gernot Kleinberger3, Miguel Angel Araque Caballero4, Michael Ewers5, 1German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; 2 Ludwig-Maximilians-University, Munich, Germany; 3 Ludwig-Maximilians-University Munich, Munich, Germany; 4Institute for Stroke and Dementia Research, M€unchen, Germany; 5Institute for Stroke and Dementia Research, Klinikum der Universitaet Muenchen, Ludwig-Maximilians-University Munich, Munich, Germany. Contact e-mail: [email protected] Background: TREM2 is a transmembrane protein selectively ex-
pressed by microglia in the central nervous system. The TREM2 ectodomain is proteolytically released as a soluble variant (sTREM2). sTREM2 in the cerebrospinal fluid (CSF) may be a candidate for a marker of microglial activity. We previously described that CSF sTREM2 is increased in early symptomatic stages of sporadic Alzheimer’s disease (AD), but nothing is known in autosomal dominant Alzheimer’s disease (ADAD). In the present study, we aimed to determine how many years before the expected symptom onset (EYO) mutation carriers (MC) of ADAD show altered CSF sTREM2 levels compared to non-carriers (NC). Methods: We analyzed data from 218 participants, including 127 MC and 91 NC siblings enrolled in the Dominantly Inherited Alzheimer Network (DIAN) initiative. In order to study the changes of CSF sTREM2 during the progression of AD, we used a linear mixed model with mutation status, EYO (and its quadratic term and the
P370
Podium Presentations: Thursday, July 28, 2016
interactions with mutation status) along with age as fixed effects, and family affiliation as random effect. To determine differences between MC and NC, we estimated the levels of CSF sTREM2 at 5-years intervals of EYO from the previous model, and subsequently compared them by t-test. Associations with the core AD CSF biomarkers were assessed using a linear regression model adjusted for gender, age and EYO. Results: CSF sTREM2 levels were significantly increased in MC compared to NC at EYO¼-10 and these difference remained significant until EYO¼ +5 years. In more advanced stages (EYO>+5), no significant differences were found. In the whole sample of subjects, higher levels of CSF sTREM2 were associated with higher levels of T-tau (b¼+0.302, p<0.0001) and P-tau181P (b¼+0.274, p¼0.0001), but no significant association was found with Ab 1-42 (b¼+0.008, p¼0.904). The positive association between CSF sTREM2 and Ttau or P-tau181Pwas present in NC and asymptomatic (CDR¼0) MC subjects but not in the symptomatic (CDR>0) MC ones. Conclusions: CSF sTREM2 levels change during disease progression of ADAD, with an increase that occurs years before the symptoms onset (possibly reflecting an early increased microglia response to neuronal injury) and is attenuated in later stages. THURSDAY, JULY 28, 2016 FEATURED RESEARCH SESSIONS F5-03 DEBATE: SHOULD BIOMARKERS EVER BE USED IN CLINICAL CARE? F5-03-01
BIOMARKERS SHOULD BE USED IN CLINICAL CARE BASED ON EXISTING EFFECTIVENESS AND ECONOMIC EVIDENCE
Michel Louis Grignon, McMaster University, Hamilton, ON, Canada. Contact e-mail: [email protected] Background: Funding agencies are allocating large amounts of their resources to support biomarker research. Methods: Commentaries and reviews were identified through a literature review. Results: Biomarkers of dementia should be used in clinical care for the four main following reasons: (1) We need biomarkers (mostly MRI) to rule out other possible causes of cognitive impairment such as strokes or brain injuries. This one is obvious and not disputed. (2) Biomarkers should be used for early detection, before Alzheimer’s disease has already brought irreversible damages to the brain. The logic of the argument is Bayesian: even though the sensitivity and specificity of existing tests are low (Noel-Storr et al. 2013), the costs of wrong diagnoses are small, and the benefits of a true positive are very large. The main reason is that prevention after early detection involves mostly lifestyle changes, that have minor side effects only. (3) Biomarkers should be used in clinical settings, because otherwise they will be used outside of the clinical encounter: individuals want to know and if the information is potentially available, they will get the information and, potentially act upon it. Insurers and employers might also force individuals to produce the information. Keeping such valuable information within the confine of the clinical encounter will be socially and clinically welfare-improving. (4) Last, current trials are too small and narrow in focus to provide good evidence on their accuracy. Real-life use of tests in clinical practice will yield the scale and scope needed for validating and improving tests. Moreover, since blinding is not achieved in trials for dementia, real-life tests will do as well as RCTs. Conclusions: Clinical care in 2016 is justified in using the available biomarkers. References:Anna Noel-Storr et al. (2013) “Systematic review of the body of evidence for the use of bio-
markers in the diagnosis of dementia”, Alzheimer’s and Dementia, 9(3), e96-e105, http://www.alz.org/research/. F5-03-02
BIOMARKERS ARE USEFUL IN TERTIARY CARE CLINICAL DECISION-MAKING
Howard H. Feldman, University of British Columbia, Vancouver, BC, Canada. Contact e-mail: [email protected] Background: Pathophysiological Alzheimer Disease (AD) bio-
markers including amyloid PET, and/or CSF measures of Abeta 1-42, total tau and phospho-tau should be used in tertiary clinical care. Methods: In the tertiary care setting, dementia specialists, in conjunction with trained radiologists at PET facilities, and/or labs with expertise in CSF assays can improve diagnostic accuracy and clinical management. There are benefits to patients and families that can be realized and now is the time to advance this diagnostic paradigm shift. Results: The clinical diagnostic accuracy of AD without pathophysiological biomarkers falls well short in sensitivity and specificity against the neuropathological gold standard. Atypical AD presentations are particularly challenging, without supportive in-vivo evidence of AD pathology. There are also 2030% of patients diagnosed AD who lack AD neuropathology1. These diagnostic challenges are amplified in trying to diagnose AD at the mild cognitive stage (MCI) when patients need vocational, social and prognostic guidance and accurate diagnosis matters. Research studies using CSF pathophysiological biomarkers achieve consistently higher AD diagnostic accuracy 2. In the tertiary care setting adding CSF biomarkers has been shown to improve diagnostic confidence, to assist diagnostic reclassification, and clinical decision making1. Conclusions: Adopting biomarkers more widely into tertiary clinical care will facilitate the necessary experience and pragmatic trials to refine their use, indications and health economic impact. References: Mouton-Liger F, Walton D, Troussiere AC et al; J.Neurol 2014, 261;144-151 2. Hansson O, Zetterberg H, Buchhave P, et al Lancet Neurol 2006; 5 (3) 228-234.
F5-03-03
‘PRIME TIME’ FOR FUNDING OF BIOMARKERS BY THIRD PARTY PAYERS AND GOVERNMENTS HAS NOT YET ARRIVED
Martin Richard John Knapp, London School of Economics and Political Science, London, United Kingdom. Contact e-mail: [email protected] Background: Enormous efforts are underway to identify biomarkers that will aid, target and improve the dementia diagnosis and treatment. Methods: Evidence is drawn from the dementia and (especially) other clinical fields on the healthcare system implications of developing and employing tests for biomarkers. Results: There are, rightly, major efforts today in many countries to ‘personalise’ how health and care systems respond to the circumstances, needs and preferences of individuals (e.g. ‘precision medicine’). But in the dementia field the state of development of biomarkers raises serious doubts about affordability and costeffectiveness, whether dementia care is funded by third party payers or governments. There are up-front costs associated with searching for any new technique or treatment; the costs of finding biomarkers, although initially mainly met by industry, will need to be recouped somewhere down the line in costs for healthcare providers and/or patients. There are the costs of the tests required to assess biomarkers; these costs could be acceptable so long as the tests are accurate and the treatments subsequently targeted are effective, available and affordable. If those tests are financially or logistically burdensome (to patients or clinicians) they could