Recommended cognitive outcomes in preclinical Alzheimer's disease: Consensus statement from the European Prevention of Alzheimer's Dementia project

The Horizon 2020/IMI European Prevention of Alzheimer's Dementia (EPAD) project will undertake large‐scale proof‐of‐concept trials in predementia Alzheimer's disease (AD). Within EPAD, the monitoring of cognitive trajectories in the preclinical period will constitute a central outcome measure; however, there are currently no clear guidelines as to how this should be achieved as most measures have been developed for the period around dementia diagnosis. The EPAD Scientific Advisory Group for Clinical and Cognitive Outcomes identified appropriate cognitive measures based on a literature search covering both cognitive correlates of preclinical brain changes from imaging studies and cognitive changes observed over time in nondementia population cohorts developing incident dementia. These measures were evaluated according to the following criteria: validity, coherence with biomarker changes, psychometric properties, cross‐cultural suitability, availability of alternative forms, and normative data limited practice effects. The resulting consensus statement provides recommendations for both future drug trials and research into preclinical Alzheimer's disease.

[1]  B. Hampstead,et al.  RBANS memory indices are related to medial temporal lobe volumetrics in healthy older adults and those with mild cognitive impairment. , 2014, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[2]  Howard J. Rosen,et al.  NIH EXAMINER: Conceptualization and Development of an Executive Function Battery , 2013, Journal of the International Neuropsychological Society.

[3]  R. Lipton,et al.  Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's disease , 2008, Journal of the International Neuropsychological Society.

[4]  H. Amièva,et al.  Prodromal Alzheimer's disease: Successive emergence of the clinical symptoms , 2008, Annals of neurology.

[5]  Andrew J Saykin,et al.  Verbal fluency performance in amnestic MCI and older adults with cognitive complaints. , 2008, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[6]  Philip S. Insel,et al.  Brain Amyloid-β Burden Is Associated with Disruption of Intrinsic Functional Connectivity within the Medial Temporal Lobe in Cognitively Normal Elderly , 2015, The Journal of Neuroscience.

[7]  P. Snyder,et al.  APOE ε4 moderates amyloid-related memory decline in preclinical Alzheimer's disease , 2015, Neurobiology of Aging.

[8]  Nick C Fox,et al.  Clinical and biomarker changes in dominantly inherited Alzheimer's disease. , 2012, The New England journal of medicine.

[9]  L. Ferrucci,et al.  Memory decline shows stronger associations with estimated spatial patterns of amyloid deposition progression than total amyloid burden , 2013, Neurobiology of Aging.

[10]  Mark A Mintun,et al.  Cognitive decline and brain volume loss as signatures of cerebral amyloid-beta peptide deposition identified with Pittsburgh compound B: cognitive decline associated with Abeta deposition. , 2009, Archives of neurology.

[11]  N. Foster,et al.  Amyloid deposition and cognition in older adults: the effects of premorbid intellect. , 2013, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[12]  Artero Sylvaine,et al.  COGNITO: Computerized Assessment of Information Processing , 2014 .

[13]  S. Leurgans,et al.  Cognitive decline in prodromal Alzheimer disease and mild cognitive impairment. , 2011, Archives of neurology.

[14]  Charles D. Smith,et al.  Prediction of preclinical Alzheimer's disease: longitudinal rates of change in cognition. , 2011, Journal of Alzheimer's disease : JAD.

[15]  Sonja Zehetmayer,et al.  Prediction of Alzheimer dementia with short neuropsychological instruments , 2009, Alzheimer's & Dementia.

[16]  Reisa A. Sperling,et al.  Face-name associative memory performance is related to amyloid burden in normal elderly , 2011, Neuropsychologia.

[17]  José Luis Molinuevo,et al.  Development of interventions for the secondary prevention of Alzheimer's dementia: the European Prevention of Alzheimer's Dementia (EPAD) project. , 2016, The lancet. Psychiatry.

[18]  S. MacDonald,et al.  Preclinical Cognitive Trajectories Differ for Alzheimer's Disease and Vascular Dementia , 2012, Journal of the International Neuropsychological Society.

[19]  C. Rowe,et al.  Decline in cognitive function over 18 months in healthy older adults with high amyloid-β. , 2013, Journal of Alzheimer's disease : JAD.

[20]  G. Alexander,et al.  Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Jennifer Weuve,et al.  Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia , 2015, Neurology.

[22]  Y. Stern,et al.  APOE genotype and cerebral blood flow in healthy young individuals. , 2003, JAMA.

[23]  C. Jack,et al.  Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers , 2013, The Lancet Neurology.

[24]  Susan M. Resnick,et al.  Trajectories of Alzheimer disease-related cognitive measures in a longitudinal sample , 2014, Alzheimer's & Dementia.

[25]  Keith A. Johnson,et al.  Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline , 2012, Neurology.

[26]  Michael W. L. Chee,et al.  Hippocampal region-specific contributions to memory performance in normal elderly , 2010, Brain and Cognition.

[27]  C. Jack,et al.  Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade , 2010, The Lancet Neurology.

[28]  Ludovico Minati,et al.  Diagnostic differentiation of mild cognitive impairment due to Alzheimer's disease using a hippocampus‐dependent test of spatial memory , 2015, Hippocampus.

[29]  Kristen M. Kennedy,et al.  Effects of beta-amyloid accumulation on neural function during encoding across the adult lifespan , 2012, NeuroImage.

[30]  Jean-François Dartigues,et al.  The 9 year cognitive decline before dementia of the Alzheimer type: a prospective population-based study. , 2005, Brain : a journal of neurology.

[31]  Elizabeth C Mormino,et al.  Subjective cognition and amyloid deposition imaging: a Pittsburgh Compound B positron emission tomography study in normal elderly individuals. , 2012, Archives of neurology.

[32]  J. Hodges,et al.  Lost in spatial translation – A novel tool to objectively assess spatial disorientation in Alzheimer's disease and frontotemporal dementia , 2015, Cortex.

[33]  K. Sathian,et al.  Activation and Effective Connectivity Changes Following Explicit-Memory Training for Face–Name Pairs in Patients With Mild Cognitive Impairment , 2011, Neurorehabilitation and neural repair.

[34]  J R Hodges,et al.  Retrosplenial cortex (BA 29/30) hypometabolism in mild cognitive impairment (prodromal Alzheimer's disease) , 2003, The European journal of neuroscience.

[35]  K. Yaffe,et al.  The projected effect of risk factor reduction on Alzheimer's disease prevalence , 2011, The Lancet Neurology.

[36]  J. Touchon,et al.  Characteristics of Alzheimer's disease patients with and without ApoE4 allele , 1996, The Lancet.

[37]  H. Amièva,et al.  The clinical picture of Alzheimer's disease in the decade before diagnosis: clinical and biomarker trajectories. , 2016, The Journal of clinical psychiatry.

[38]  T. Hedden,et al.  Meta-analysis of amyloid-cognition relations in cognitively normal older adults , 2013, Neurology.

[39]  R. Mayeux,et al.  Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease , 2013, Nature Neuroscience.

[40]  Charles Hall,et al.  Free and Cued Selective Reminding Identifies Very Mild Dementia in Primary Care , 2010, Alzheimer disease and associated disorders.

[41]  P. Lewczuk,et al.  Hippocampal volume differences between healthy young apolipoprotein E ε2 and ε4 carriers. , 2011, Journal of Alzheimer's disease : JAD.

[42]  C. Berr,et al.  Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors , 2010, BMJ : British Medical Journal.

[43]  C. Randolph,et al.  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): Utility in detection and characterization of mild cognitive impairment due to Alzheimer's disease. , 2013, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[44]  R. Brzustowicz.  Combined Trigeminal and Glossopharyngeal Neuralgia , 1955, Neurology.

[45]  C. Rowe,et al.  Imaging β-amyloid burden in aging and dementia , 2007, Neurology.