Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup

The pathophysiological process of Alzheimer’s disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long “preclinical” phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer’s Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from “normal” cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommen

[1]  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.

[2]  Douglas Galasko,et al.  Increased Cerebrospinal Fluid F2-Isoprostanes are Associated with Aging and Latent Alzheimer’s Disease as Identified by Biomarkers , 2011, NeuroMolecular Medicine.

[3]  D A Bennett,et al.  Relation of cognitive activity to risk of developing Alzheimer disease , 2007, Neurology.

[4]  Nick C Fox,et al.  Revising the definition of Alzheimer's disease: a new lexicon , 2010, The Lancet Neurology.

[5]  S. DeKosky,et al.  Ten-year incidence of dementia in a rural elderly US community population , 2000, Neurology.

[6]  C. Jack,et al.  11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment. , 2008, Brain : a journal of neurology.

[7]  Suzanne Craft,et al.  The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. , 2009, Archives of neurology.

[8]  G. Schellenberg,et al.  Dementia and Alzheimer disease incidence: a prospective cohort study. , 2002, Archives of neurology.

[9]  Keith A. Johnson,et al.  Amyloid Deposition Is Associated with Impaired Default Network Function in Older Persons without Dementia , 2009, Neuron.

[10]  Karl Herrup,et al.  Reimagining Alzheimer's Disease—An Age-Based Hypothesis , 2010, The Journal of Neuroscience.

[11]  Nick C. Fox,et al.  The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging and Alzheimer's Association workgroup , 2011 .

[12]  C R Jack,et al.  Serial MRI and CSF biomarkers in normal aging, MCI, and AD , 2010, Neurology.

[13]  R Brookmeyer,et al.  Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. , 1998, American journal of public health.

[14]  D. Geschwind,et al.  Biochemical markers in persons with preclinical familial Alzheimer disease , 2008, Neurology.

[15]  R. Petersen,et al.  Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects , 2009, Annals of neurology.

[16]  Gina N. LaRossa,et al.  [11C]PIB in a nondemented population , 2006, Neurology.

[17]  Paul Maruff,et al.  β-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease , 2007 .

[18]  J. Schneider,et al.  Neuropathology of older persons without cognitive impairment from two community-based studies , 2006, Neurology.

[19]  Jeffrey A. James,et al.  Frequent amyloid deposition without significant cognitive impairment among the elderly. , 2008, Archives of neurology.

[20]  Shaomin Li,et al.  Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory , 2008, Nature Medicine.

[21]  D. Bennett,et al.  Chronic Psychological Distress and Risk of Alzheimer’s Disease in Old Age , 2006, Neuroepidemiology.

[22]  Yaakov Stern,et al.  Cognitive Reserve: Implications for Assessment and Intervention , 2013, Folia Phoniatrica et Logopaedica.

[23]  J. Morris Early-stage and preclinical Alzheimer disease. , 2005, Alzheimer disease and associated disorders.

[24]  J. Price,et al.  Cerebral amyloid deposition and diffuse plaques in ``normal'' aging , 1996, Neurology.

[25]  G. Alexander,et al.  Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease , 2009, Proceedings of the National Academy of Sciences.

[26]  C. Rowe,et al.  Aβ deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer's disease , 2008, Neuropsychologia.

[27]  Cindee M. Madison,et al.  Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. , 2009, Brain : a journal of neurology.

[28]  L. Hebert,et al.  Cognitive activity and the cognitive morbidity of Alzheimer disease , 2010, Neurology.

[29]  C. Rowe,et al.  Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease , 2011, Annals of neurology.

[30]  Li-Huei Tsai,et al.  Amyloid-Independent Mechanisms in Alzheimer's Disease Pathogenesis , 2010, The Journal of Neuroscience.

[31]  Keith A. Johnson,et al.  Cognition, Reserve, and Amyloid Deposition in Normal Aging , 2009, Annals of neurology.

[32]  J. Trojanowski,et al.  Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people. , 2010, Archives of neurology.

[33]  Majaz Moonis,et al.  Amyloid Deposition Begins in the Striatum of Presenilin-1 Mutation Carriers from Two Unrelated Pedigrees , 2007, The Journal of Neuroscience.

[34]  C. Jack,et al.  11 C PiB and structural MRI provide complementary information in imaging of Alzheimer ’ s disease and amnestic mild cognitive impairment , 2008 .

[35]  Keith A. Johnson,et al.  Amyloid deposition and brain volume across the continuum of aging and Alzheimer's Disease , 2009, Alzheimer's & Dementia.

[36]  S. Rubin,et al.  Predictors of maintaining cognitive function in older adults , 2009, Neurology.

[37]  J. Morris,et al.  The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals , 2008, Cerebral cortex.

[38]  Sachin Dixit,et al.  APOE4 Allele Disrupts Resting State fMRI Connectivity in the Absence of Amyloid Plaques or Decreased CSF Aβ42 , 2010, The Journal of Neuroscience.

[39]  L A Beckett,et al.  Age-specific incidence of Alzheimer's disease in a community population. , 1995, JAMA.

[40]  C. Rowe,et al.  Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging , 2010, Neurobiology of Aging.

[41]  D. Pollen,et al.  Familial Alzheimer disease: Decreases in CSF Aβ42 levels precede cognitive decline , 2005, Neurology.

[42]  I. Sokal,et al.  CSF tau/Aβ42 ratio for increased risk of mild cognitive impairment , 2007, Neurology.

[43]  G. Schellenberg,et al.  CSF tau/Abeta42 ratio for increased risk of mild cognitive impairment: a follow-up study. , 2007, Neurology.

[44]  R. Green,et al.  Epidemiology of apathy in older adults: the Cache County Study. , 2007, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[45]  M. Mintun,et al.  Brain volume decline in aging: evidence for a relation between socioeconomic status, preclinical Alzheimer disease, and reserve. , 2008, Archives of neurology.

[46]  D. Selkoe Alzheimer's Disease Is a Synaptic Failure , 2002, Science.

[47]  Hiroko H Dodge,et al.  Depressive symptoms and cognitive decline in late life: a prospective epidemiological study. , 2006, Archives of general psychiatry.

[48]  P. Matthews,et al.  Distinct patterns of brain activity in young carriers of the APOE e4 allele , 2009, NeuroImage.

[49]  Keith A. Johnson,et al.  Imaging amyloid deposition in Lewy body diseases , 2008, Neurology.

[50]  A. Fagan,et al.  Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. , 2007, Archives of neurology.

[51]  Hwamee Oh,et al.  β-Amyloid affects frontal and posterior brain networks in normal aging , 2011, NeuroImage.

[52]  D. Bennett,et al.  Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. , 2004, Archives of neurology.

[53]  Hyoung-Gon Lee,et al.  Challenging the Amyloid Cascade Hypothesis: Senile Plaques and Amyloid‐β as Protective Adaptations to Alzheimer Disease , 2004, Annals of the New York Academy of Sciences.

[54]  Paul Maruff,et al.  Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. , 2007, Brain : a journal of neurology.

[55]  Michael W. Weiner,et al.  Selective Disruption of the Cerebral Neocortex in Alzheimer's Disease , 2010, PloS one.

[56]  A. Fagan,et al.  Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. , 2009, Archives of neurology.

[57]  D. Head,et al.  Amyloid Plaques Disrupt Resting State Default Mode Network Connectivity in Cognitively Normal Elderly , 2010, Biological Psychiatry.

[58]  C. Jack,et al.  MRI and CSF biomarkers in normal, MCI, and AD subjects , 2009, Neurology.

[59]  Tamara B Harris,et al.  Association of plasma beta-amyloid level and cognitive reserve with subsequent cognitive decline. , 2011, JAMA.

[60]  M. Albert,et al.  Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[61]  Nick C Fox,et al.  Increased brain atrophy rates in cognitively normal older adults with low cerebrospinal fluid Aβ1‐42 , 2010, Annals of neurology.

[62]  A. Dale,et al.  Brain atrophy in healthy aging is related to CSF levels of Aβ1-42. , 2010, Cerebral cortex.

[63]  M. Albert,et al.  Introduction to Revised Criteria for the Diagnosis of Alzheimer ’ s Disease : National Institute on Aging and the Alzheimer Association Workgroups , 2011 .

[64]  Gina N. LaRossa,et al.  Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Aβ42 in humans , 2006, Annals of neurology.

[65]  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.

[66]  Bradley T. Hyman,et al.  Distribution of Alzheimer‐type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease , 1992, Neurology.

[67]  L. Ferrucci,et al.  Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB , 2010, Neurology.

[68]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup , 2011 .

[69]  Pierrick Bourgeat,et al.  Independent contribution of temporal beta-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease. , 2011, Brain : a journal of neurology.

[70]  Jessica C. Payne-Murphy,et al.  Trajectory of mild cognitive impairment onset , 2008, Journal of the International Neuropsychological Society.

[71]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

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

[73]  J. Morris,et al.  Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease , 2010, Science.