Baseline MRI Predictors of Conversion from MCI to Probable AD in the ADNI Cohort

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.

Progranulin levels in blood in Alzheimer's disease and mild cognitive impairment

“…As such, mild cognitive impairment (MCI)–defined by focal memory or executive function deficits not explained by age, without dementia or loss of day‐to‐day function – has become a major focus of study 18. MCI patients convert to AD at a rate of 10–15% per year 19, 20. However, the majority of MCI patients will not transition to dementia, and some may display spontaneous improvement 19.…”

“…However, the majority of MCI patients will not transition to dementia, and some may display spontaneous improvement 19. Currently, estimates of hippocampal or entorhinal cortex volume coupled with cognitive function testing are the best predictors of disease transition 20, 21. However, reconstructive MRI imaging is expensive and not easily transferable to community hospitals.…”

Grey-matter volume as a potential feature for the classification of Alzheimer’s disease and mild cognitive impairment: an exploratory study

“…It has been widely applied to the study of regional grey-matter alterations in various disorders [14][15][16][17][18][19][20][21] . The medial temporal lobe (including the hippocampus and parahippocampus) most consistently exhibits decreased grey-matter volume in AD and MCI [12,16,17,[22][23][24][25][26][27][28][29][30] .…”

A Disease State Fingerprint for Evaluation of Alzheimer's Disease

“…Diverse sets of neuropsychological tests and biomarkers have been investigated for their efficacy to predict conversion from MCI to AD [7][8][9][10][11], and several studies have shown that combining results can yield even better predictions [12][13][14]. Increased knowledge about cognitive tests and biomarkers has influenced a recent proposal for a new lexicon, where the term AD encompasses the whole spectrum of the disease from predementia to dementia phases and further emphasizes the combination of clinical and biomarker data [15].…”