Alzheimer's Disease Neuroimaging Initiative (ADNI)

Background: Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging and mild cognitive impairment (MCI) and need to be evaluated longitudinally. Objective: To characterize cross-sectionally and longitudinally clinical measures in normal controls, subjects with MCI, and subjects with mild Alzheimer disease (AD) to enable the assessment of the utility of neuroimaging and chemical biomarker measures. Methods: A total of 819 subjects (229 cognitively normal, 398 with MCI, and 192 with AD) were enrolled at baseline and followed for 12 months using standard cognitive and functional measures typical of clinical trials. Results: The subjects with MCI were more memory impaired than the cognitively normal subjects but not as impaired as the subjects with AD. Nonmemory cognitive measures were only minimally impaired in the subjects with MCI. The subjects with MCI progressed to dementia in 12 months at a rate of 16.5% per year. Approximately 50% of the subjects with MCI were on antidementia therapies. There was minimal movement on the Alzheimer's Disease Assessment Scale–Cognitive Subscale for the normal control subjects, slight movement for the subjects with MCI of 1.1, and a modest change for the subjects with AD of 4.3. Baseline CSF measures of Aβ-42 separated the 3 groups as expected and successfully predicted the 12-month change in cognitive measures. Conclusion: The Alzheimer's Disease Neuroimaging Initiative has successfully recruited cohorts of cognitively normal subjects, subjects with mild cognitive impairment (MCI), and subjects with Alzheimer disease with anticipated baseline characteristics. The 12-month progression rate of MCI was as predicted, and the CSF measures heralded progression of clinical measures over 12 months.

[1]  R. Reitan.  Validity of the Trail Making Test as an Indicator of Organic Brain Damage , 1958 .

[2]  P. Rubé,et al.  L’examen Clinique en Psychologie , 1959 .

[3]  J. Ware,et al.  Random-effects models for longitudinal data. , 1982, Biometrics.

[4]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.

[5]  E. Kaplan,et al.  The Boston naming test , 2001 .

[6]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[7]  K. Davis,et al.  A new rating scale for Alzheimer's disease. , 1984, The American journal of psychiatry.

[8]  M. D. O'Brien,et al.  Cerebral blood flow in dementia , 1986, Neurology.

[9]  C. Reynolds,et al.  Wechsler memory scale-revised , 1988 .

[10]  Robert A. Bornstein,et al.  The Wechsler Memory Scale—Revised , 1990 .

[11]  M. Mega,et al.  The Neuropsychiatric Inventory , 1994, Neurology.

[12]  John Hardy,et al.  Amyloid, the presenilins and Alzheimer's disease , 1997, Trends in Neurosciences.

[13]  Jon A. Wellner,et al.  A Hybrid Algorithm for Computation of the Nonparametric Maximum Likelihood Estimator from Censored Data , 1997 .

[14]  J. Hardy,et al.  The presenilins and Alzheimer's disease. , 1997, Human molecular genetics.

[15]  C. Jack,et al.  Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment , 1999, Neurology.

[16]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[17]  R. Petersen.  Mild cognitive impairment as a diagnostic entity , 2004, Journal of internal medicine.

[18]  L. Thal,et al.  A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment , 2005, Neuropsychopharmacology.

[19]  Wang Li-juan.  Donepezil and Vitamin E for the Treatment of Mild Cognitive Impairment , 2005 .

[20]  C. Jack,et al.  Alzheimer's Disease Neuroimaging Initiative , 2008 .

[21]  P. Murali Doraiswamy,et al.  Alzheimer's Disease: 100 Years of Progress , 2005 .

[22]  D. Bennett,et al.  Vitamin E and donepezil for the treatment of mild cognitive impairment. , 2005, The New England journal of medicine.

[23]  E. Tangalos,et al.  Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia. , 2006, Archives of neurology.

[24]  E. Tangalos,et al.  Neuropathologic features of amnestic mild cognitive impairment. , 2006, Archives of neurology.

[25]  H. Vinters.  Neuropathology of amnestic mild cognitive impairment. , 2006, Archives of neurology.

[26]  R. Petersen,et al.  Mild cognitive impairment , 2006, The Lancet.

[27]  K. Blennow,et al.  Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study , 2006, The Lancet Neurology.

[28]  Neuroimaging Clinics of North America: Alzheimer’s Disease–100 Years of Progress, Vol. 15, No. 4 , 2007, American Journal of Neuroradiology.

[29]  Nick C Fox,et al.  Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study , 2007, The Lancet Neurology.

[30]  J. Trojanowski,et al.  Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics , 2007, Nature Reviews Drug Discovery.

[31]  Geert Molenberghs,et al.  Random Effects Models for Longitudinal Data , 2010 .

[32]  Safety and efficacy of galantamine in subjects with mild cognitive impairment , 2010, Neurology.