Clinical Core of the Alzheimer's Disease Neuroimaging Initiative: progress and plans

Abstract

The Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI) has provided clinical, operational, and data management support to ADNI since its inception. This article reviews the activities and accomplishments of the core in support of ADNI aims. These include the enrollment and follow-up of more than 800 subjects in the three original cohorts: healthy controls, amnestic mild cognitive impairment (now referred to as late MCI, or LMCI), and mild Alzheimer's disease (AD) in the first phase of ADNI (ADNI 1), with baseline longitudinal, clinical, and cognitive assessments. These data, when combined with genetic, neuroimaging, and cerebrospinal fluid measures, have provided important insights into the neurobiology of the AD spectrum. Furthermore, these data have facilitated the development of novel clinical trial designs. ADNI has recently been extended with funding from an NIH Grand Opportunities (GO) award, and the new ADNI GO phase has been launched; this includes the enrollment of a new cohort, called early MCI, with milder episodic memory impairment than the LMCI group. An application for a further 5 years of ADNI funding (ADNI 2) was recently submitted. This funding would support ongoing follow-up of the original ADNI 1 and ADNI GO cohorts, as well as additional recruitment into all categories. The resulting data would provide valuable data on the earliest stages of AD, and support the development of interventions in these critically important populations.

Figure 1

Trajectories of biomarkers during the progression of AD. This hypothetical graph is designed to capture the following points: 1. CSF Aβ₄₂ and amyloid PET, reflecting amyloid accumulation in brain, move in tandem. 2. Amyloid accumulation precedes cognitive and functional decline by years, and changes only gradually once symptoms develop. 3. Compared to CSF Aβ₄₂ and amyloid PET, CSF tau, MRI volumes and FDG-PET are more dynamic biomarkers of disease progression across the spectrum of AD neurobiology. 4. Cognitive decline becomes evident at the onset of EMCI, and accelerates as the disease progresses. 5. Functional decline becomes evident at the onset of dementia, and accelerates as the disease progresses. 6. All of these points are conjectural to varying degrees; they require confirmation with long-term longitudinal follow-up in ADNI 2 and beyond. [Reprinted from Lancet Neurology, 2010, with modifications.]