Abstract
The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a multi-center study assessing neuroimaging in diagnosis and longitudinal monitoring. Amnestic Mild Cognitive Impairment (MCI) often represents a prodromal form of dementia, conferring a 10-15% annual risk of converting to probable AD. We analyzed baseline 1.5T MRI scans in 693 participants from the ADNI cohort divided into four groups by baseline diagnosis and one year MCI to probable AD conversion status to identify neuroimaging phenotypes associated with MCI and AD and potential predictive markers of imminent conversion. MP-RAGE scans were analyzed using publicly available voxel-based morphometry (VBM) and automated parcellation methods. Measures included global and hippocampal grey matter (GM) density, hippocampal and amygdalar volumes, and cortical thickness values from entorhinal cortex and other temporal and parietal lobe regions. The overall pattern of structural MRI changes in MCI (n=339) and AD (n=148) compared to healthy controls (HC, n=206) was similar to prior findings in smaller samples. MCI-Converters (n=62) demonstrated a very similar pattern of atrophic changes to the AD group up to a year before meeting clinical criteria for AD. Finally, a comparison of effect sizes for contrasts between the MCI-Converters and MCI-Stable (n=277) groups on MRI metrics indicated that degree of neurodegeneration of medial temporal structures was the best antecedent MRI marker of imminent conversion, with decreased hippocampal volume (left > right) being the most robust. Validation of imaging biomarkers is important as they can help enrich clinical trials of disease modifying agents by identifying individuals at highest risk for progression to AD.
Highlights
Alzheimer’s disease (AD) is the most common neurodegenerative illness associated with aging, accounting for 6070% of age-related dementia cases
No significant differences in mean Geriatric Depression Scale (GDS) scores were found between the Mild Cognitive Impairment (MCI)-Stable, MCI-Converter, and AD groups
We examined baseline 1.5T T1-weighted magnetic resonance imaging (MRI) scans from 693 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort to (1) characterize initial differences between the AD, MCI, and HC groups and (2) detect anatomic features associated with imminent conversion from MCI to probable AD within one year (MCIConverters)
Summary
Alzheimer’s disease (AD) is the most common neurodegenerative illness associated with aging, accounting for 6070% of age-related dementia cases. Characterization of the earliest known clinical signs has led to the development of the classification of Mild Cognitive Impairment (MCI), which is thought to be a transitional stage between normal aging and the development of AD [3]. Patients with MCI, those with primary memory deficits or “amnestic MCI”, have a significantly higher likelihood to progress to probable AD, with a conversion rate of 10-15% per year [4]. MCI represents an important clinical group in which to study longitudinal changes associated with the development of AD. The detection of subtle changes in brain structure associated with disease progression and the development of tools to detect those who are most likely to convert from MCI to probable AD is an important goal
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