Background & Rationale

Alzheimer’s Disease (AD) is an irreversible neurodegenerative disease that results in a loss of mental function due to the deterioration of brain tissue. It is the most common cause of dementia among people over the age of 65, affecting an estimated 5.3 million Americans, yet no prevention methods or cures have been discovered. For more information about Alzheimer’s disease, visit the Alzheimer’s Association. The goal of the ADNI study is to track the progression of the disease using biomarkers to assess the brain’s structure and function over the course of four disease states. The ADNI study will assess participants in the following stages:

ADNI Participant Stages across ADNI 1/GO/2

CN Normal Aging /Cognitively Normal ADNI 1/GO/2 CN participants are the control subjects in the ADNI study. They show no signs of depression, mild cognitive impairment or dementia.
SMC Significant Memory Concern ADNI 2 SMC participants score within normal range for cognition (or CDR = 0) but indicate that they have a concern, and exhibit slight forgetfulness. The informant does not equate this as progressive memory impairment nor considers this as consistent forgetfulness.
EMCI Early Mild Cognitive Impairment ADNI GO/2 MCI participants have reported a subjective memory concern either autonomously or via an informant or clinician. However, there are no significant levels of impairment in other cognitive domains, essentially preserved activities of daily living and there are no signs of dementia. Levels of MCI (early or late) are determined using the Wechsler Memory Scale Logical Memory II.
MCI Mild Cognitive Impairment ADNI 1
LMCI Impairment ADNI GO/2
AD Alzheimer’s disease ADNI 1/GO/2 AD participants have been evaluated and meet the NINCDS/ADRDA criteria for probable AD.

ADNI 2 has added a new cohort, the Significant Memory Concern (SMC).  Subjective memory concerns have been shown to be correlated with a higher likelihood of progression, thereby minimizing the stratification of risk among normal controls and addressing the gap between healthy elderly controls and MCI. The key inclusion criteria that distinguish the Significant Memory Concern cohort are a self-report significant memory concern from the participant, quantified by using the Cognitive Change Index and the Clinical Dementia Rating (CDR) of zero.

About Biomarkers

A biomarker, or biological marker, is a substance, measurement or indicator of a biological state. Biomarkers may exist before clinical symptoms arise. ADNI uses various biomarkers to help predict the onslaught of Alzheimer’s disease.

The graph on the right depicts biomarkers as indicators of dementia. The curves indicate changes caused by five studied biomarkers:

  1. Amyloid beta imaging detected in CSF and PET amyloid imaging
  2. Neurodegeneration detected by rise of CSF tau species and synaptic dysfunction, measured via FDG-PET
  3. Brain atrophy and neuron loss measured with MRI (most notably in hippocampus, caudate nucleus, and medial temporal lobe)
  4. Memory loss measured by cognitive assessment
  5. General cognitive decline measured by cognitive assessment

Changes 1-3 are indicated by biomarkers that can be observed prior to a dementia diagnosis. Items 4-5 are the classic indicators of dementia diagnosis.